ImportanceAppropriate use of antibiotics is life-saving in neonatal early-onset sepsis (EOS), but overuse of antibiotics is associated with antimicrobial resistance and long-term adverse outcomes. Large international studies quantifying early-life antibiotic exposure along with EOS incidence are needed to provide a basis for future interventions aimed at safely reducing neonatal antibiotic exposure.ObjectiveTo compare early postnatal exposure to antibiotics, incidence of EOS, and mortality among different networks in high-income countries.Design, Setting, and ParticipantsThis is a retrospective, cross-sectional study of late-preterm and full-term neonates born between January 1, 2014, and December 31, 2018, in 13 hospital-based or population-based networks from 11 countries in Europe and North America and Australia. The study included all infants born alive at a gestational age greater than or equal to 34 weeks in the participating networks. Data were analyzed from October 2021 to March 2022.ExposuresExposure to antibiotics started in the first postnatal week.Main Outcomes and MeasuresThe main outcomes were the proportion of late-preterm and full-term neonates receiving intravenous antibiotics, the duration of antibiotic treatment, the incidence of culture-proven EOS, and all-cause and EOS-associated mortality.ResultsA total of 757 979 late-preterm and full-term neonates were born in the participating networks during the study period; 21 703 neonates (2.86%; 95% CI, 2.83%-2.90%), including 12 886 boys (59.4%) with a median (IQR) gestational age of 39 (36-40) weeks and median (IQR) birth weight of 3250 (2750-3750) g, received intravenous antibiotics during the first postnatal week. The proportion of neonates started on antibiotics ranged from 1.18% to 12.45% among networks. The median (IQR) duration of treatment was 9 (7-14) days for neonates with EOS and 4 (3-6) days for those without EOS. This led to an antibiotic exposure of 135 days per 1000 live births (range across networks, 54-491 days per 1000 live births). The incidence of EOS was 0.49 cases per 1000 live births (range, 0.18-1.45 cases per 1000 live births). EOS-associated mortality was 3.20% (12 of 375 neonates; range, 0.00%-12.00%). For each case of EOS, 58 neonates were started on antibiotics and 273 antibiotic days were administered.Conclusions and RelevanceThe findings of this study suggest that antibiotic exposure during the first postnatal week is disproportionate compared with the burden of EOS and that there are wide (up to 9-fold) variations internationally. This study defined a set of indicators reporting on both dimensions to facilitate benchmarking and future interventions aimed at safely reducing antibiotic exposure in early life.
Tg infection during pregnancy and congenital disease are more frequent in non-native mothers and their infants. Measures to prevent Tg exposition must be carefully explained to pregnant women, with a focus on specific habits in non-native women. Prenatal screening is still effective to select women for prenatal therapy aiming to decrease vertical transmission and to identify foetuses/newborns with congenital disease that could benefit from pre/postnatal antiparasitic therapy.
Caprine herpesvirus type 1 (CpHV-1), like other members of the alpha subfamily of herpesviruses, establishes latent infections in trigeminal ganglion neurons. Our groups previously demonstrated that CpHV-1 induces apoptosis in goat peripheral blood mononuclear cells and in an epithelial bovine cell line, but the ability of CpHV-1 to induce apoptosis in neuronal cells remains unexplored. In this report, the susceptibility of Neuro 2A cells to infection by CpHV-1 was examined. Following infection of cultured cells with CpHV-1, expression of cell death genes was evaluated using real-time PCR and Western blot assays. Analysis of virus-infected cells revealed activation of caspase-8, a marker for the extrinsic pathway of apoptosis, and caspase-9, a marker for the intrinsic pathway of apoptosis at 12 and 24 h post-infection. Significant increase in the levels of cleaved caspase-3 was also observed at the acme of cytopathic effect at 24 h post-infection. In particular, at 3 and 6 h post-infection, several proapototic genes were under-expressed. At 12 h post-infection several proapototic genes such as caspases, TNF, Cd70, and Traf1 were over expressed while Bcl2a1a, Fadd, and TNF genes were underexpressed. In conclusion, the simultaneous activation of caspase-8 and caspase-9 suggests that CpHV-1 can trigger the death-receptor pathway and the mitochondrial pathway separately and in parallel. Our findings are significant because this is the first published study showing the effect of CpHV-1 infection in neuronal cells in terms of gene expression and apoptosis modulation.
Aim: To develop a methodology for direct detection of high risk human papillomavirus (HPV) Recently the association between HPV and cervical neoplasia has been questioned because HPV sequences are demonstrable using the polymerase chain reaction (PCR) in cervical samples from a high proportion of normal women.`2 However, interpretation of the data has been problematic due to inconsistencies in methodology and results from different laboratories. Estimates of the prevalence of HPV infection in both normal and abnormal cervical epithelial cells have varied widely."2 The possibility of contamination with exogenous HPV sequences is difficult to exclude when methods are used which require destruction of cellular morphology. In situ hybridisation has the advantage that cellular localisation of sequences can be performed microscopically and it excludes the possibility of contamination. Isotopic detection of HPV in cervical smears has been previously described'3 and non-isotopic in situ hybridisation (NISH) has been performed on cell samples collected by cervicovaginal lavage.'4 These methods are not, however, applicable to cervical smears collected in the routine way. Methods PROBESGenomic probes for HPV 6, i 115, 16
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